During normal cardiac function, the left ventricle fills during two diastolic phases, a passive filling phase and an active filling phase. The passive filling phase occurs first as the ventricle relaxes following ventricular systole. Ventricular relaxation causes the pressure within the left ventricle to fall, allowing the mitral valve between the left atrium and left ventricle to open. Blood flows into the left ventricle through the left atrium during the passive filling phase due to the pressure difference across the mitral valve. As the passive filling rate slows, the left atrium contracts, actively contributing to ventricular filling. The force generated by the actively contracting left atrium forces more blood into the ventricle.
This atrial contribution to ventricular filling is important in maintaining an adequate preload for optimal ventricular contraction. According to the Frank-Starling law, the ventricles contract more forcefully during systole when filled to a greater degree during diastole. Generally, cardiac stroke volume increases as cardiac filling increases. During many disease states or during various physiologic conditions such as exercise, an overlap between the phases of active atrial contraction and passive left ventricular filling can occur. This can result in reduced atrial contribution to ventricular filling as the pressure gradient across the mitral valve is reversed from normal upon the onset of systole. This contributes to aphysiologic conditions including mitral regurgitation and flow reversal through the pulmonary vein, manifesting itself with a clinical symptom referred to as “pacemaker syndrome”. If atrial contraction occurs too late after the passive filling phase, ventricular contraction may have already begun, closing the mitral valve. Thus, late atrial contraction may cause the atria to contract against a closed or partially closed valve, which can result in retrograde flow. Early atrial contraction, prior to the end of the passive filling phase, results in fusion of the passive and active filling phases. The force available from the contracting atria is under-utilized when blood is forced into an empty or only partially filled ventricle. This reduces the overall filling of the left ventricle and results in reduced effectiveness of systolic contraction.
During a number of cardiac stimulation therapies, including dual chamber pacing, cardiac resynchronization therapy, and extra-systolic stimulation among others, an atrial-ventricular (AV) delay is set to control the timing between atrial depolarization and ventricular depolarization. The AV delay can be optimized based on various hemodynamic measurements which are aimed at improving either diastolic or systolic function but may or may not improve both diastolic and systolic function. The AV delay is commonly optimized using echocardiography for maximizing left ventricular filling time while ensuring that the atrial contribution to diastolic filling is not truncated.
A physician's criteria for determining a patient's optimal left AV delay is often based on the patient's underlying disease and symptoms. The patient's symptoms mitigated after an AV delay optimization procedure are therefore dependent on the individual patient's disease, cardiac contractile function or physiologic compensatory mechanisms. The patient's disease and functional state may be associated with systolic or diastolic dysfunction and this information is utilized clinically to determine the various pacing therapy parameters that should be optimized in an attempt to achieve the greatest patient benefit. Furthermore, an AV delay setting determined to be optimal during an office visit may change over time due to changes in disease state, patient activity level, medications or other influences. Other timing parameters, such as AA delays and VV delays may also impact diastolic and systolic function and therefore may be optimized to achieve a desired benefit of a particular pacing therapy. Optimization of one timing parameter may influence the optimal value of another timing parameter.